The role of SWI/SNF in HIV-1 chromatin remodeling

If you type the keyword “SWI/SNF chromatin remodeling” and “HIV-1” in PubMed, less than 20 research articles appear on your screen. Actually, the topic of nucleosome remodeling of HIV-1 provirus is less than 10 years old. The more we investigate HIV-1, the more we know that the connection between host chromatin and HIV-1 pathogenesis cannot be ignored.

The integration of HIV-1 provirus into the cellular genome is an essential mechanism for the establishment of stable infection. After this step, how the HIV-1 provirus further manipulates chromosomal features to continue its life cycle is therefore considered important. SWI/SNF is one of the main actors involved in the alteration of DNA accessibility within repressive nucleosomes. In fact, back in 1996, the SWI/SNF regulator has been found in the RNA polymerase II holoenzyme and has been reported to be involved in chromatin remodeling [1]. Later, it was realized that the SWI/SNF complex found in both eukaryotes and prokaryotes is actually a group of proteins that associate to remodel the nucleosome state (active or repressive). SWI/SNF contains either Brahma (BRM) or the closely related BRG1 as its catalytic subunit and shares most common subunits [2]. In addition to taking the responsibility for chromatin remodeling, functions of the SWI/SNF complex are also involved in many aspects of cellular processes, including development, cancer as well as stem cell biology.

The first research article that built up the bridge between SWI/SNF chromatin remodeling and HIV-1 has been shown by Henderson et al. [3] in 2004. At present, the SWI/SNF complex is not defined to be involved in the Tat-dependent mechanism for HIV-1 provirus access through the nucleosome (nuc-1); however, it serves as a cofactor, or let’s say “Tat interactome”, for Tat transactivation of the HIV-1 promoter [4]. A current model has been proposed by Bukrinsky (2006) in Retrovirology [5]: Tat binds to newly synthesised TAR RNA following initiation of transcription from the HIV-1 promoter; meanwhile, several cellulcar transcriptional factors, including p300, pTEFb and RNA polymerase II are recuited by the interaction with HIV-1 integrase-interacting protein 1 (Ini1) and the BRM-type SWI/SNF complex which leads to initiate remodeling of nuc-1 (Fig. A). Subsequently, Tat lysine 50 is acetylated by p300, which forces Tat to dissociate from TAR and creates a new binding site for another SWI/SNF catalytic subunit, BRG-1. The new recruited BRG-1-type SWI/SNF complex therefore completes remodeling (disrupted) of nuc-1 and allows the efficient elongation of transcription (Fig. B).

Our current knowledge regarding the chromatin remodeling of HIV-1 is just the tip of the iceberg. In addition to the SWI/SNF complex, there are probably many unknown factors involved in this mechanism. Sooner or later, we need to rely on more sensitive technologies than ChIP to write a new chapter for this story.



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